Vaginal epithelial tissue has been shown to be receptive to drugs delivered by many different therapeutic formulations. However, there exists a problem of adequately and accurately targeting the delivery of these drugs, including therapeutic agents such as those used for contraception or for the prevention of infection by the human immunodeficiency virus (HIV) or by other sexually transmitted infections (STI). Additionally, it is difficult to maintain therapeutic agents in place on vaginal surfaces and replenish deleted areas with a fresh agent. Vaginal gels, foaming tablets, and creams are messy in application and prone to leakage. This problem is further complicated by the fact that an ideal location for topical therapeutic vaginal drug delivery is commonly at or near the woman's cervix. There exists a need for a convenient method that a woman can use that is safe and effective in keeping a delivered therapeutic formulation in the vagina at or near a desired target area for a specified/sufficient time period.
While it is known that every woman can theoretically locate and touch her cervix, many women have never done this and are not confident of their ability to place a diaphragm or cervical cap correctly over the cervix. Placement of gels, creams and foaming tables using a traditional applicator has additional limitations.
In addition to the conventional application of gels, foaming tablets, creams, diaphragms and cervical caps referred to above, prior attempts to deliver drugs via the vaginal surfaces have included tampon or tampon-like delivery systems. Some of these devices, for example, the devices of U.S. Pat. Nos. 5,201,326 and 6,086,909, are dry-absorbent tampons having external surfaces treated with dry materials that can be released when the tampon absorbs menses. One primary obstacle to the use of these devices is that the absorbent nature of these tampons makes it extremely difficult for the tampon to serve the dual purpose of delivering a therapeutic benefit while simultaneously absorbing menses. A therapeutic agent originally present on the dry surface of the tampon is likely to be carried into the body of the absorbent tampon rather than towards vaginal surfaces as the tampon absorbs menses. Consequently, the delivery of a therapeutic agent by this method is unpredictable, generally requiring a large dose of the agent on the tampon surface. This is undesirable from both economic and safety standpoints.
Other tampon-like drug delivery systems, for example, those shown in U.S. Pat. Nos. 3,921,636; 3,933,073 and U.S. Application 2003/0163103, utilize absorbent tampons that deliver drugs at controlled rates to the vagina via microdiffusion. These devices store drugs in microcapsules or within a permeable membrane for controlled release into the vagina, which is triggered by body heat or moisture. The microdiffusion approach is problematic because it deals with the controlled release of very small quantities of a drug from an essentially dry tampon and programmed by the diffusive nature of the microporous materials containing the drug. The rate of diffusion cannot be increased or decreased according to an instantaneous need from the surrounding vaginal tissue. Another U.S. Pat. No. 3,921,636, specifies that the drug be in non-crushable media to avoid device damage before use, but this can create discomfort when the product is worn.
Another class of devices includes those described in U.S. Pat. Nos. 4,320,759; 4,576,604; and 4,786,500 wherein tampon-like drug delivery devices deliver therapeutic formulations to the vaginal walls via osmosis. A principal drawback of these devices is that they deliver small quantities of concentrated drugs at a very slow rate and could never be expected to provide the quantities of a beneficial, therapeutic agent which could quickly coat the vaginal surfaces with, for example, a spermicidal formulation for prevention of pregnancy. For such a purpose, the device might be inserted only a few minutes prior to sexual intercourse and rapid delivery of the therapeutic agent would be required.
Attempts have been made to develop tampons as drug delivery systems by incorporating small quantities of a concentrated therapeutic agent on and/or within a dry-compressed tampon. Unfortunately, if it is used intra-menstrually (i.e., when there is no menstrual flow), there is insufficient vaginal wetness to cause the tampon to expand. Furthermore, it is risky and medically unacceptable to insert a dry tampon when a woman is not menstruating, as it can predispose the woman to irritation, discomfort, epithelial tearing, and possibly to toxic shock syndrome. Under normal menstrual conditions, the insertion of a dry, compressed tampon results in its expansion by wetting with menses. As it absorbs menses, any incorporated therapeutic agent dissolves in the surrounding vaginal tissue (U.S. Pat. No. 5,201,326). Unfortunately, the concentration of the therapeutic agent delivered varies both between and within individual tampon insertions due to the non-homogenous nature of menses and the differing amounts of menses present to dissolve regions of the embedded therapeutic agent into, rather than out of, the tampon.
Yet another type of medicated tampon device has been reported—a dry, compressed, absorbent tampon pretreated with small quantities of bactericides or antivirals. For example, U.S. Pat. No. 5,000,749 teaches the use of iodine. However, in this and similar products, the intent is that the therapeutic agent remain within the tampon during use in order to deal with a problem that can be caused by the tampon, such as the proliferation of bacteria that occurs in the triggering of toxic shock syndrome. The iodine prevents Staphylococcus aureus from growing within the tampon and consequently prevents the creation and absorption of bacterial toxins by the surrounding vaginal tissue.
Other disclosed devices (e.g., U.S. Application 2001/000993A1) cover the addition of flowable therapeutic formulations to dry, compressed tampons. They are useful for postoperative management of cervical surgery. This is more complicated in that it requires the user to inject a therapeutic agent into each tampon, causing the tampon to expand. Subsequent insertion of this treated tampon into the vagina is complicated by the premature expansion of the tampon. Additionally, release of the added therapeutic agent is retarded by the absorbent nature of the compressed tampon. Dry, compressed tampons are intended to absorb and retain flowable therapeutic formulations, not to reproducibly dispense them to the surrounding vaginal tissue. For example, Pauletti in U.S. Application 2003/0049302 A1 describes the use of a conventional compressed, absorbent tampon with an attached mucoadhesive composition containing a topical vaginal or systemic cancer therapy agent. This mucoadhesive composition adheres to the vaginal tissue, facilitating the long-term absorption of the contained therapeutic agents.
Purely mechanical means of introducing flowable therapeutic formulations into the vagina require the incorporation of a rupturable sac within a tampon (U.S. Application 2003/0153864). Alternatively, this rupturing of the capsule can be initiated by body temperature melting the capsule (U.S. Application 2003/0191439). Such devices are difficult to manufacture and vary in their ability to deliver uniform therapy.
Harrison (U.S. Pat. No. 6,086,909) also discloses a tampon intended to carry a drug into the vagina with the intention that the drug be absorbed transvaginally during menstruation. The design of the tampon and the location of the embedded drug are configured to permit the absorption of menses without contaminating or interfering with the release and transvaginal absorption of the drug released from the tampon. This invention shares the limitations described above for similar devices.
Thus, there is a need for a vaginal drug delivery system and method that overcome the limitations of the prior art in a manner which results in an economical design for dispensing flowable therapeutic formulations onto the vaginal surfaces irrespective of the conditions present in the vagina.